Our overall objectives are to characterize and study the mode of action of regulatory factors produced by nonantigen specific T suppressor cells. These T cells, which show no apparent antigen specificity, have been found in a variety of diseases and can most easily be generated for study in vitro by exposure to the mitogen Concanavalin A. A major drawback to elucidating the nature of their suppression, however, is the heterogeneity of cells resulting from mitogen activation. We intend to utilize hybridomas produced from these T cells to examine their suppressive activity in well-defined systems measuring T-\and B-cell activation. The physicochemical nature of isolated factors and binding specificity for cell surface determinants will be examined. We shall ask whether distinct factors inhibit the secretion of defined lymphokines (B cell signals) from cloned functional T helper cells or inhibit T cells at a particular point in the cell cycle during activation. In particular, we shall determine whether additional molecules inhibit specific B-cell subpopulations at either stages of proliferation or differentiation and whether inhibition is dependent on the nature of the triggering signal to the B cell. (SR)